Small SNPs, Big Effects: A Review of Single Nucleotide Variations and Polymorphisms in Key Genes Associated With Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterised by significant genetic variation. This article examines genetic alterations linked to ASD, with a specific emphasis on single nucleotide polymorphisms (SNPs) and single nucleotide variants (SNVs). Recent genome-wide association studies (GWAS) have identified several genetic variations associated with ASD. Although their precise roles remain unclear, such genetic polymorphisms and variations significantly influence several neurodevelopmental processes. Mutations in SHANK3 and NRXN1, for example, disrupt synaptic activity and neurotransmission, contributing to ASD and intellectual deficits. Similarly, PTEN and MECP2, crucial for brain development, are associated with abnormal cell proliferation and neurodevelopmental disorders when mutated. CHD8, a key regulator of chromatin remodelling, is strongly linked to ASD, with its mutations impacting transcriptional regulation and neurodevelopment, while mutations in SCN2A disrupt neuronal excitability and synaptic transmission. In this review, we discuss SNPs and SNVs across these six key genes, to summarise their impact on the aetiology of ASD. A shift of focus in autism genetics giving equal importance to minor variations is critical to better understand the intricate aetiology of ASD and to create specific treatment strategies.